Impact of state and trait anxiety severity on retention and phase advancement in an outpatient buprenorphine treatment program.

BACKGROUND AND OBJECTIVES: Comorbid anxiety is common among buprenorphine patients and may lead to poorer outcomes. This study aimed to examine the prevalence and impact of anxiety severity, measured by the State-Trait Anxiety Inventory (STAI) form Y-1 & Y2 scale, on treatment outcomes (retention and phase advancement) among outpatient buprenorphine-treated patients. METHODS: A retrospective chart review of 94 patients admitted to an outpatient buprenorphine treatment program was conducted. Patients were dichotomized into high and low severity groups based upon an STAI State Anxiety (S-Anxiety) and STAI Trait Anxiety (T-Anxiety) score ≥60 and <60, respectively. Associations of anxiety severity on successful phase advancement and retention during the first 90 days of treatment were assessed. RESULTS: Twenty-one of 94 (22%) participants reported high S-Anxiety and had a significantly greater likelihood of phase advancement (OR = 12.80, 95% CI = [1.19, 136.71]) than those with low S-Anxiety. No significant associations were found between either S-Anxiety or T-Anxiety and treatment retention. Current alcohol use and UDS negative test results for THC or amphetamines were each associated with phase advancement. THC negative UDS test results were associated with 90-day treatment retention. DISCUSSION AND CONCLUSIONS: Contrary to prior reports, buprenorphine patients with higher state anxiety severity demonstrated similar retention and more rapid phase advancement than those with lower state anxiety severity. SCIENTIFIC SIGNIFICANCE: To our knowledge, this is the first study to quantify current anxiety severity using the STAI scale and evaluate its impact on treatment outcomes among buprenorphine-treated patients.

Development and validation of a rapid liquid chromatography/tandem mass spectrometry method to quantitate gabapentin and buprenorphine in human serum.

RATIONALE: Gabapentin has shown initial promise as an opioid-sparing medication in pain patients as well as a treatment for opioid withdrawal and liquid chriomatography/tandem mass spectrometry (LC/MS/MS) is often used for clinical monitoring. Despite reports of validated tandem mass spectrometric methods for the determination of gabapentin and buprenorphine, mechanisms for the collision-induced fragmentation have not been adequetely described. METHODS: A rapid analytical method has been developed to determine gabapentinoid, gabapentin, and the partial opioid agonist, buprenorphine, in 20 µL of human serum using LC/MS/MS with a chromatographic run time of 2 min. A simplified sample cleanup procedure using methanol precipitation of serum proteins/lipids followed by evaporation and reconstitution in mobile phase was demonstrated. Gabapentin and buprenorphine were detected following positive ion electrospray ionization using multiple-reaction monitoring. The internal standard approach was used for quantitation with labeled gabapentin-D10 and buprenorphine-D4 serving as internal standards. Using organic reaction principals and stable isotope labels, collision-induced fragmentation mechanisms for both gabapentin and buprenorphine are proposed. The method was validated according to the FDA Guidance for Industry - Bioanalytical Method Validation. RESULTS: Accuracy was demonstrated by error values ≤15% for buprenorphine and ≤6% for gabapentin. The inter-day precision was ≤4.88% and 15.59% for gabapentin and buprenorphine and the intra-day precision was ≤5.20% and 11.65% for gabapentin and buprenorphine. The lower limit of quantitation corresponded to 10 ng/mL for gabapentin and 1 ng/mL for buprenorphine in serum. Recoveries were 104 ± 2.55% and 85 ± 2.03% for gabapentin and buprenorphine, respectively. CONCLUSIONS: Concentrations of gabapentin and buprenorphine were determined for five authentic human serum samples to further validate the utility of the method and applicable to therapeutic drug monitoring beyond its use as a drug screening assay. Furthermore, new mechanisms for the collision-induced dissociation of gabapentin and buprenorphine have been proposed.

Intramuscular medication for treatment of agitation in the emergency department: A systematic review of controlled trials.

BACKGROUND: Severely agitated patients in the emergency department (ED) are often sedated with intramuscularly-administered medications. The evidence base underlying particular medication choices is surprisingly sparse, as existing reviews either have methodological limitations or have included data collected outside of emergent settings. OBJECTIVES: The objective of this review was to examine all controlled trials in emergent settings that have used standardized scales to measure the effectiveness of intramuscular medication for the treatment of acute agitation. METHODS: This review was registered in Prospero as CRD42018105745. PubMed, International Pharmaceutical Abstracts, Web of Science, PsycINFO, and clinicaltrials.gov were searched for prospective controlled trials investigating intramuscular antipsychotics for agitation. Articles were assessed for bias across five domains using the revised Cochrane Risk of Bias Tool. RESULTS: Eight studies were eligible for inclusion in the systematic review, none of which had a low risk of bias. Five studies had a moderate risk of bias with heterogenous designs, populations, and treatments. These studies seemed to suggest that second generation antipsychotics (SGAs) likely reduce agitation as effectively as first generation antipsychotics (FGAs) plus an adjunctive medication with similar or lower risk of side effects. CONCLUSIONS: Existing trials on the use of intramuscular antipsychotics in the ED/psychiatric ED setting were small, heterogenous, and at a moderate or high risk of bias. Given the clinical importance of this topic, further prospective investigations are desperately needed but are currently unfeasible under Food and Drug Administration Exception From Informed Consent regulations.

Adherence to guideline creation recommendations for suicide prevention in the emergency department: A systematic review.

OBJECTIVES: Suicide rates in the United States rose 35.2% from 1999-2018. As emergency department (ED) providers often have limited training in management of suicidal patients and minimal access to mental health experts, clinical practice guidelines (CPGs) may improve care for these patients. However, clinical practice guidelines that do not adhere to quality standards for development may be harmful both to patients, if they promote practices based on flawed evidence, and to ED providers, if used in malpractice claims. In 2011, the Institute of Medicine created standards to determine the trustworthiness of CPGs. This review assessed the adherence of suicide prevention CPGs, intended for the ED, to these standards. Secondary objectives were to assess the association of adherence both with first author/organization specialty (ED vs non-ED) and with inclusion of recommendations on substance use, a potent risk factor for suicide. METHODS: This is a systematic review of available suicide-prevention CPGs for the ED in both peer-reviewed and gray literature. This review followed the PRISMA standards for reporting systematic reviews. RESULTS: Of 22 included CPGs, the 7 ED-sponsored CPGs had higher adherence to quality standards (3.1 vs 2.4) and included the highest-rated CPG (ICAR2E) identified by this review. Regardless of specialty, nearly all CPGs included some mention of identifying or managing substance use. CONCLUSIONS: Most suicide prevention CPGs intended for the ED are written by non-ED first authors or organizations and have low adherence to quality standards. Future CPGs should be developed with more scientific rigor, include a multidisciplinary writing group, and be created by authors working in the practice environment to which the CPG applies.

The utility of a statewide prescription drug-monitoring database vs the Current Opioid Misuse Measure for identifying drug-aberrant behaviors in emergency department patients already on opioids.

BACKGROUND: The most recent guidelines on prescribing opioids from the United States Centers for Disease Control recommend that clinicians not prescribe opioids as first-line therapy for chronic non-cancer pain. If an opioid prescription is considered for a patient already on opioids, prescribers are encouraged to check the statewide prescription drug monitoring database (PDMP). Some additional guidelines recommend screening tools such as the Current Opioid Misuse Measure (COMM) which may also help identify drug-aberrant behaviors. OBJECTIVE: To compare the PDMP and the Current Opioid Misuse Measure (COMM), a commonly-recommended screening tool for patients on opioids, in detecting drug-aberrant behaviors in patients already taking opioids at the time of ED presentation. METHODS: Patients on opioids were enrolled prospectively in a mixed urban-suburban ED seeing approximately 65,000 patients per year. The sensitivity, specificity, likelihood ratios, and diagnostic odds ratios of the PDMP and COMM were compared against objective criteria of drug-aberrant behaviors as documented in the electronic medical record (EMR) and medical examiner databases. RESULTS: Compared to the COMM, the PDMP had similar sensitivity (36% vs 45%) and similar specificity (79% vs 55%), but better positive predictive value, better negative predictive value, and better diagnostic odds ratio. The combination of the PDMP and the COMM did not improve the detection of drug-aberrant behaviors. CONCLUSIONS: The PDMP alone is a more useful as a screening instrument than either the COMM or the combination of the PDMP plus COMM in patients already taking opioids at time of ED presentation. However, the PDMP misses a majority of patients with documented drug-aberrant behaviors in the EMR, and should not be used in isolation to justify whether a particular opioid prescription is appropriate.

Screening Tools Validated in the Outpatient Pain Management Setting Poorly Predict Opioid Misuse in the Emergency Department: A Pilot Study.

BACKGROUND: Currently, no universally accepted methods exist to assess drug-related aberrant behaviors in emergency department (ED) patients. There are several screening tools to identify opioid misuse in patients with chronic pain, however, the validity of these screening tools to assess for misuse within the ED remains unclear. OBJECTIVES: This study investigated the effectiveness of three commonly used screening tools, previously validated in outpatient pain management settings, to assess risk of opioid misuse in ED patients. METHODS: This was a prospective observational study of 154 participants (median age 50 years; 49.6% female) presenting to an academic ED for a chief complaint of pain ≥ 6 months or an opioid refill request. Participants completed the Opioid Risk Tool, the Screener and Opioid Assessment for Patients with Pain-Revised, and the Current Opioid Misuse Measure. Scores for each were compared with electronic medical record (EMR) data alone or a reference standard comprising EMR + statewide prescription drug monitoring program (PDMP) + medical examiner database. RESULTS: Using the combined reference standard, 55.8% of participants displayed at least one aberrant behavior. Regardless of the reference standard, the test characteristics of these screening tools were modest at best, with likelihood ratios close to 1. CONCLUSION: Three screening tools previously validated in outpatient pain management settings poorly categorized risk among ED patients with chronic noncancer pain or requests for opioid refills, and should not be used to assess drug-aberrant behaviors in the ED. Review of the EMR alone or together with the PDMP may be more useful methods to assess drug-aberrant behaviors in the ED setting.

Moderators of response to sertraline versus placebo among recently abstinent, cocaine dependent patients: A retrospective analysis of two clinical trials.

BACKGROUND AND OBJECTIVES: Moderators of treatment response to serotonin reuptake inhibitor sertraline (SRT) for cocaine dependence were assessed in two randomized, double blind, placebo-controlled clinical trials. METHODS: Generalized estimating equation modeling was performed on data from cocaine-dependent volunteers randomized to receive SRT or placebo (N = 126) who completed >2-week drug-free residential portions of the 12-week trials, in which subsequent outpatient treatment (weeks 3-12) included weekly cognitive behavioral therapy and thrice-weekly supervised urine toxicology. PRIMARY OUTCOME MEASURE: Relapse (2 consecutive cocaine-positive or missing urines) following residential stay. Potential moderators included treatment, sex, age, race, depression measures, baseline cocaine urine result, and alcohol dependence diagnosis (ADDx). RESULTS: Odds ratios (OR) for relapse showed placebo-treated participants were significantly more likely to relapse than SRT participants. Regardless of treatment condition, participants more likely to relapse were male, and those with lower Hamilton depression ratings, or baseline cocaine-negative urines. Older subjects or those with current ADDx had higher relapse risk than those without ADDx; however, treating older or ADDx participants with SRT reduced cocaine relapse more than placebo. DISCUSSION AND CONCLUSIONS: Women or those with more severe cocaine use or depressive symptoms may have fewer cocaine relapses regardless of medication treatment. SRT at 200 mg reduced cocaine relapse more than placebo, especially in older participants or in those with comorbid ADDx. SCIENTIFIC SIGNIFICANCE: SRT may be efficacious to support relapse prevention among cocaine-dependent patients in the context of brief residential followed by outpatient treatment, especially in older participants or those with comorbid alcohol/cocaine dependence. (Am J Addict 2017;26:807-814).

Telemedicine Interest for Routine Follow-Up Care Among Neurology Patients in Arkansas.

BACKGROUND: Teleneurology in Arkansas has been used primarily for management of acute stroke with a state-funded hub-and-spoke model allowing physicians at rural hospitals to access vascular neurologists in time to facilitate tissue plasminogen activator administration. Routine neurologic care has been provided only in small pilot studies. We wished to determine patient interest in participating in teleneurology for routine follow-up visits as well as demographic and medical factors associated with interest. MATERIALS AND METHODS: New and established patients of the Neurology Outpatient Clinic at the University of Arkansas for Medical Sciences (UAMS) were surveyed between March 2011 and December 2012 to assess their interest in participating in teleneurology as well as potential factors associated with their interest. RESULTS: Of 1,441 respondents, 52.4% were interested in telemedicine. Of those interested versus uninterested in telemedicine, respectively, 68.9% versus 36.32% traveled more than 1 h to the clinic, 64.7% versus 35.3% had difficulty secondary to neurological conditions, 22.6% versus 6.8% had missed medical appointments due to travel problems, and 43.1% versus 9.4% had travel-imposed financial hardship. CONCLUSIONS: Telemedicine interest for routine follow-up visits was strong among patients at the UAMS Neurology Outpatient Clinic. Factors positively associated with interest included long travel distances, travel expenses, and transportation difficulties. These results suggest that implementing a telemedicine program for follow-up visits would be acceptable to neurology patients for routine ongoing care.

Clinical efficacy of sertraline alone and augmented with gabapentin in recently abstinent cocaine-dependent patients with depressive symptoms.

BACKGROUND: Cocaine dependence is a major public health problem with no available robustly effective pharmacotherapy. This study's aim was to determine if treatment with sertraline (SERT) or SERT plus gabapentin (GBP) improved treatment retention, depressive symptoms, and/or cocaine use. METHODS: Depressed cocaine-dependent patients (N = 99) were enrolled in a 12-week, double-blind, randomized, placebo (PLA)-controlled, clinical trial and placed in research beds at a residential treatment facility (Recovery Centers of Arkansas). They were randomized by depressive symptom severity and inducted onto 1 of the following while residing at the Recovery Centers of Arkansas: SERT (200 mg/d), SERT (200 mg/d) plus GBP (1200 mg/d), or PLA. Participants transferred to outpatient treatment at the start of their third week, continued receiving study medications or PLA (weeks 3-12), and participated in weekly individual cognitive behavioral therapy. Compliance was facilitated through the use of contingency management procedures. Supervised urine samples were obtained thrice weekly and self-reported mood weekly. At the end of 12 weeks, participants were tapered off the study medication over 5 days and referred to a local treatment program. RESULTS: Sertraline, but not SERT plus GBP, showed a significantly lower overall percentage of cocaine-positive urine samples compared with that of PLA. A significantly greater percentage of participants experienced relapse in the PLA group (88.9%) compared with that of the SERT group (65.2%). Hamilton depression ratings decreased significantly over time regardless of the treatment group. Retention in treatment did not differ significantly between the treatment groups. CONCLUSIONS: Sertraline plus GBP may not be superior to SERT alone in delaying relapse among abstinent cocaine-dependent individuals undergoing cognitive behavioral therapy.

Smoking status affects cognitive, emotional and neural-connectivity response to distress-inducing auditory feedback.

BACKGROUND: An important motive for cigarette smoking and impediment to cessation success is the avoidance of affective distress. Low levels of distress tolerance have been linked to smoking behavior, cessation history, smoking characteristics, and risk of recurrence among people who smoke. A better understanding of the neural mechanisms underlying distress sensitivity could inform approaches to help reduce avoidance of affective distress during smoking cessation. Previously among healthy participants, low distress tolerance on an MRI version of the Paced Auditory Serial Addition Task (PASAT-M), which induces distress via negative auditory feedback, was associated with larger differences in task-based functional connectivity (TBFC) between the auditory seed region and the anterior insula. METHODS: Here, we tested differences in task performance and TBFC during affective distress among people who smoke (Smoke; n = 31) and people who quit smoking (Ex-smoke; n = 31). RESULTS: Smoke had poorer task accuracy and reported a steeper increase in negative mood from the easy to distress blocks. Smoke had a larger difference in connectivity (distress > easy condition) between the auditory seed region and the left inferior frontal gyrus and right anterior insula. Additionally, task accuracy positively correlated with the difference in connectivity (distress > easy condition) with the left inferior frontal gyrus and the right anterior insula among Smoke but not Ex-smoke. CONCLUSIONS: These results are consistent with the idea that people who smoke are more sensitive to cognitive-affective distress and that the inferior frontal gyrus and anterior insula play important roles in the regulation of distress.

Characteristics of patients undergoing medication-assisted -treatment for opioid use disorder and their interest in Tai Chi practice.

OBJECTIVES: (1) To explore the characteristics of patients with opioid use disorder (OUD) maintained on either methadone or buprenorphine and (2) to determine the relative acceptability of integrating Tai Chi (TC) practice into an ongoing medication-assisted treatment for opioid use disorder (MOUD) program. DESIGN: Survey study. SETTING: The University of Arkansas for Medical Sciences Center for Addiction Services and Treatment Program. PATIENTS: 97 patients receiving MOUD treatment. MAIN OUTCOMES: Drug use history, treatment status, physical limitation, mental health, pain, and whether participants were interested in using TC to improve health outcomes. RESULTS: At least 30.9 percent of the sample reported moderate or higher level of limitation in performing rigorous physical activities, pain intensity, and pain interference. Between 37.1 and 61.5 percent of the sample reported various psychiatric symptoms. Methadone patients reported higher levels of physical limitations, especially in rigorous activities (p = .012), climbing several flights of stairs (p = .001), and walking more than a mile (p = .011), but similar levels of pain (ps = .664-.689) and psychiatric symptoms (ps = .262-.879) relative to buprenorphine patients. At least 40.2 percent of participants expressed moderate or higher level of interest in TC for improving health outcomes, with methadone patients more interested in participating to ease mental and sleep problems (p = .005) and improve physical fitness (p = .015) compared to buprenorphine patients. CONCLUSIONS: High prevalence of physical limitation, pain, and psychiatric comorbidities were found in OUD patients. Since patients were interested in TC to improve their health outcomes, this low-cost intervention, if proven effective, can be integrated into ongoing MOUD programs to improve health in this population.

Acceptability of a Game-Based Intervention to Prevent Adolescent Prescription Opioid Misuse.

Objective: This study assessed the initial acceptability of SafeUse, a game-based opioid misuse prevention intervention for delivery via smartphone among adolescents. Evidence-based educational and refusal skills training materials were adapted, and game design elements were applied to clinically and scientifically informed scenarios in which opioids are typically introduced to adolescents using standard product development methods to create the SafeUse prototype. Materials and Methods: In a mixed-methods study, 14 adolescents were assessed on their knowledge and perceptions of opioids before and following 5-7 days of access to SafeUse. Participants provided feedback in focus groups on the acceptability, relevance, and understandability of SafeUse and made suggestions for its improvement. Feedback was coded and summarized as to playability, acceptability, appropriateness, content development, and knowledge transfer. Pre- and post-access quantitative data were analyzed using Wilcoxon matched pairs signed-rank tests. Results: Overall, participants liked SafeUse, its characters, graphics, and approach, finding it more appealing than lectures/reading materials and appropriate for school settings. They moderately to extremely "liked the game," "would like to play more game modules," "liked playing through the decisions," thought the game was realistic/relevant and fun, and they learned new information about opioids. Participants reported increased confidence to refuse opioids and decreased likelihood of accepting opioids from someone they know. Knowledge about opioids increased (P < 0.006), and adolescent perception that prescription drugs are safer than illegal drugs decreased (P < 0.003) after playing SafeUse. Conclusion: Findings suggest that SafeUse is acceptable and likely educational to adolescents and worthy of further development and research.

Characterizing methamphetamine withdrawal in recently abstinent methamphetamine users: a pilot field study.

BACKGROUND: Methamphetamine dependence has become a significant problem, but methamphetamine withdrawal symptoms have not been well studied. METHODS: This prospective observational pilot study was designed to examine withdrawal symptoms, mood, anxiety, cognitive function, and subjective measures of sleep over a 4-week period in six patients entering residential treatment for methamphetamine dependence. RESULTS: Methamphetamine withdrawal symptoms, mood, and anxiety symptoms all resolve fairly quickly within 2 weeks of cessation of methamphetamine. Sleep was disrupted over the course of the 4-week study. No clinically significant alterations in blood pressure or heart rate were identified. This study did not demonstrate any alterations in cognitive function over the 4 weeks of the residential stay. CONCLUSIONS: This pilot study points toward the need for a double-blind, placebo-controlled amphetamine withdrawal paradigm in humans where changes in sleep, cognitive function, and withdrawal measures can be explored more fully. SCIENTIFIC SIGNIFICANCE: This study extends the literature by pointing toward a methamphetamine withdrawal syndrome that includes alterations in measures of sleep quality and refreshed sleep, early improvement in depression and anxiety symptoms, most striking during the first week, but persisting into the second week.

Utility of a controlled amphetamine withdrawal paradigm among adults who use methamphetamine: A pilot clinical trial.

BACKGROUND: The continued increase in prevalence of methamphetamine use in the United States has resulted in a significant increase in the number of patients entering treatment for methamphetamine use. However, no robustly efficacious pharmacologic treatment for methamphetamine use or withdrawal has been identified to date after stopping methamphetamine use. AIMS: Given the association between methamphetamine withdrawal and relapse during early treatment, this study tested a controlled d-amphetamine withdrawal paradigm among methamphetamine-using individuals. METHODS: Treatment-seeking adults who used methamphetamine (N = 34; 47% female; 100% white) were enrolled in a 4-week, randomized, double-blind, placebo-controlled trial in a residential setting, in which all participants were maintained on d-amphetamine (30 mg BID) during week 1, then half were switched to placebo during weeks 2-3. All participants received placebo during week 4. Outcomes included vital signs, withdrawal, cravings for methamphetamine, mood, and cognition. Bivariate analyses tested treatment group differences on baseline demographic and outcome variables. Repeated measures models examined main and interaction effects of treatment over time. RESULTS/OUTCOMES: Participants were successfully randomized and safely stabilized on d-amphetamine. Craving for methamphetamine increased during weeks 2-3 in the placebo group relative to those on d-amphetamine. Interactions with age and heart rate were noted. CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first double-blind, placebo-controlled trial measuring pharmacologic effects of abruptly stopping controlled d-amphetamine administration in adults who use methamphetamine. Results support the potential of this withdrawal paradigm to further examine the efficacy of pharmacologic agents in ameliorating methamphetamine withdrawal symptoms.

Behavioral effects of gamma-hydroxybutyrate in humans.

Despite the therapeutic use and abuse potential of gamma-hydroxybutyrate (GHB or Xyrem), relatively few studies have examined the behavioral effects of GHB in humans under controlled laboratory conditions. Thus, this eight-session study examined in 10 non-substance-abusing volunteers the behavioral effects of GHB at each of the following doses: 0, 0.32, 0.56, 0.75, 1.0, 1.8, 2.4, 3.2 g/70 kg, orally. Order of dose testing was random, except that the first two participants received active doses in ascending order and 2.4 g/70 kg was always tested before 3.2 g/70 kg. Before drug administration and at several postdrug time points, self-report, observer report, physiological, and psychomotor performance measures were obtained. Analyses based on area under the curve showed that GHB produced dose-related increases in subjective ratings of sedative-like, stimulant-like, positive mood, and dissociative effects, but no changes in psychomotor performance measures or blood pressure. Analyses based on peak effects generally showed dose-related increases in ratings indicating sedative-like, dissociative, and drug liking, although some measures showed U-shaped dose-related changes. These initial findings suggest that GHB at doses of 0.32-3.2 g/70 kg produces dissociative, sedating and some stimulant-like effects in humans without a history of sedative abuse.

Effect of PTSD diagnosis and contingency management procedures on cocaine use in dually cocaine- and opioid-dependent individuals maintained on LAAM: a retrospective analysis.

This randomized clinical trial retrospectively examined the effect of post-traumatic stress disorder (PTSD) and contingency management (CM) on cocaine use in opioid and cocaine dependent individuals maintained on high or low-dose LAAM randomly assigned to CM or a yoked-control condition. Cocaine-positive urines decreased more rapidly over time in those without PTSD versus those with PTSD in the noncontingency condition. In participants with PTSD, CM resulted in fewer cocaine-positive urines compared to the noncontingent condition. This suggests that CM may help improve the potentially worse outcomes in opioid- and cocaine-dependent individuals with PTSD compared to those without PTSD. (Am J Addict 2010;00:1-9).

Feasibility and Preliminary Efficacy of Isradipine During Outpatient Buprenorphine Stabilization and Detoxification: A Pilot Randomized, Placebo-Controlled Trial.

BACKGROUND: Given the immense burden of the widespread use of opioids around the world, exploring treatments that improve drug use outcomes, and craving and withdrawal measures in individuals with opioid use disorder is crucial. This pilot study examined the feasibility and preliminary efficacy of the L-type calcium-channel blocker isradipine (ISR) to improve drug use outcomes, and craving and withdrawal measures during buprenorphine (BUP)/ISR stabilization and subsequent taper in opioid-dependent individuals. METHODS: Participants were stabilized on BUP sublingual tablets within the first 2 days of week 1, were then randomized and inducted on either ISR or placebo, gradually increasing the dose over the next 2 weeks, followed by a 10-day BUP taper during weeks 5-6, and ISR/placebo taper during weeks 7 to 8. Assessments included thrice-weekly measures of craving and withdrawal, as well as vital signs and urine drug screens. Medication compliance was assessed by monitoring number of missed clinic visit days. RESULTS: Baseline characteristics of participants (n = 25; 60% male, 96% Caucasian, 48% employed, mean age 32.8 years) did not differ significantly between treatment groups (isradipine, n = 11; placebo, n = 14). During the stabilization phase (n = 19), ISR participants had significantly lower rates of illicit opioid-positive urines (treatment × visit: t = -2.16, P = 0.03), as well as reduction in craving intensity (t = -2.50, P = 0.01), frequency (t = -3.43, P < 0.01) and duration (t = -2.51, P = 0.01). ISR was well tolerated with mild adverse effects. CONCLUSIONS: This study was likely underpowered due to being a pilot trial. Although preliminary results suggest ISR may improve BUP-assisted treatment outcomes, concerns about high number of exclusions (n = 11 during taper phase) based on cardiovascular measures as well as ISR-induced changes in vital signs with the immediate release formulation may limit the feasibility of this approach. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01895270. Registered 10 July 2013, https://clinicaltrials.gov/ct2/show/NCT01895270?id=NCT01895270&draw=2&rank=1.

Open-label pilot study of modafinil for methamphetamine dependence.

Methamphetamine has become a major public health issue globally, particularly in the United States. Despite this, no effective pharmacotherapy for methamphetamine abuse has been developed to date. This 6-week, open-label pilot clinical trial examined the safety and tolerability of modafinil up to 400 mg/d in 8 methamphetamine-dependent individuals. Subjects were inducted onto modafinil at 400 mg/d for more than 3 days and remained on 400 mg/d for 4.5 weeks. Participants received weekly blister packs and underwent weekly individual cognitive behavioral therapy. Adjunctive contingency management procedures were used to enhance retention. Vital signs and supervised urine samples were obtained thrice weekly, and self-reported drug use and Hamilton anxiety and depression ratings were completed once weekly. Eight subjects (50% female, 100% white, aged 35-52 years) were enrolled. Four completed the 6-week study, 3 completed a portion, and 1 withdrew consent before completing intake. Results showed that systolic blood pressure (t = 1.09, P = 0.28), diastolic blood pressure, (t = 1.18, P = 0.24), and heart rate (t = 1.55, P = 0.13) did not change over time. Scores on the modafinil side effects checklist (t = -2.63, P = 0.01), Hamilton anxiety scale (t = -2.50, P = 0.018), and Hamilton depression scale (t = -3.25, P = 0.003) all decreased over time. The proportion of urine positive for amphetamines did not change over time (t = -0.52, P = 0.61), whereas self-reported methamphetamine use did (t = -2.86, P < 0.005). These results suggest that modafinil at 400 mg/d is safe and tolerable for methamphetamine-dependent individuals.